3'H-Cycloprop[15,16]androsta-6,15-dien-17-one, 3-(2,2-dimethyl-1-oxopropoxy)-15,16-dihydro-5-hydroxy-, (3.beta.,5.beta.,15.alpha.,16.alpha.)-

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

other information

Study period:

Mar 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well reported GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

no bacteria strain included to detect cross-linking mutagens

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

5-hydroxy-15β,16β-methylene-3β-pivaloyloxy-5β-androst-6-en-17-one

EC Number:

617-345-3

Cas Number:

82543-14-4

Molecular formula:

C25H36O4

IUPAC Name:

5-hydroxy-15β,16β-methylene-3β-pivaloyloxy-5β-androst-6-en-17-one

Details on test material:

- Name of test material (as cited in study report): ZK 90504
- Batch No.: 21608604

Method

Target gene:

Histidine gene locus

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 1535, TA 100, TA 1537, TA 1538, TA 98

Metabolic activation:

with and without

Metabolic activation system:

liver S9-mix from Aroclor 1254 -treated rats

Test concentrations with justification for top dose:

Enpivalat: six concentrations from 0.1 to 5 mg/plate
Sodium azide: 5 µg/plate (TA 1535 and TA 100, without S9 mix)
2-Nitrofluorene: 10 µg/plate (TA 1538 and TA 98, without S9 mix)
4-Nitro-o-phenylenediamine: 10 µg/plate (TA 1537, without S9 mix)
Benzo[a]pyrene: 2.5 µg/plate (TA 100 and TA 98, with S9 mix)
Cyclophosphamide: 400 µg/plate (TA 1535, with S9 mix)
2-Aminoanthracene: 2 µg/plate (with S9 mix)

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Sodium azide (TA 1535 and TA 100, -S9 mix), 2-Nitrofluorene (TA 1538 and TA 98, -S9 mix), 4-NPDA (TA 1537, -S9 mix), Benzo[a]pyrene (TA 100 and TA 98, + S9 mix), Cyclophosphamide (TA 1535, +S9 mix), 2-Aminoanthracene (+S9 mix)

Results and discussion

Test results

Species / strain:

other: Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538, TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Growth inhibition was observed at the highest dose tested. Precipitates in the agar were found starting at 2.5 mg/plate onwards.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Executive summary:

Enpivalat was tested in the Salmonella/microsome test for point-mutagenic effects in doses up to 5000 µg/plate on the five histidine-auxotrophic Salmonella typhimurium LT2 strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98.

A cytotoxic effect was seen at the highest dose tested (5 mg/plate). Precipitates in the agar were also detectable starting at 2.5 mg/plate.

There was no evidence for a mutagenic activity of Enpivalat, when tested up to the highest recommended dose level of 5.0 mg/plate in the absence and presence of S9 mix.